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genetic signatures of ERCC1 and ERCC2 expression,along with SNPs variants,unveil favorable prognosis in SCLC patients undergoing platinum-based chemotherapy

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Oncology Research 2025年第1期33卷 45-55页

作者： ENRICO CALIMAN SARA FANCELLI FEDERICO SCOLARI ADRIANO PASQUI CLARA MANNESCHI DANIELE LAVACCHI FRANCESCA MAZZONI FRANCESCA GENSINI VALERIA PASINI CAMILLA EVA COMIN LUCA VOLTOLINI SERENA PILLOZZI LORENZO ANTONUZZO Clinical Oncology Unit Careggi University HospitalFlorence50134Italy Department of Experimental and Clinical Medicine University of FlorenceFlorence50134Italy Department of Health Sciences University of FlorenceFlorence50134Italy Medical Oncology Unit Careggi University HospitalFlorence50134Italy Department of Experimental and Clinical Biomedical Sciences“Mario Serio” University of FlorenceFlorence50134Italy section of Anatomic Pathology Department of Health SciencesUniversity of FlorenceFlorence50139Italy section of Surgery Histopathology and Molecular PathologyUniversity of FlorenceFlorence50139Italy Thoracic Surgery Unit Careggi University HospitalFlorence50134Italy

Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum *** in this repair mechanism may affect patients’*** and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to *** expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor ***:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy *** with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant ***:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.

关键词： Small cell lung cancer(SCLC) Nucleotide excision repair(NER)pathway ERCC genes Single nucleotide polymorphisms(SNPs) Platinumchemotherapy(CT)

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Post-transcriptional regulation of MicroRNA Accumulation and Function： New Insights from Plants

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Molecular Plant 2018年第8期11卷 1006-1007页

作者： Zofia Szweykowska-Kulinska Artur Jarmolowski Department of gene expression Institute of Molecular Biology and Biotechnology Faculty of Biology Adam Mickiewicz University Poznan Umultowska 89 Poznan 61-614 Poland

MicroRNAs （miRNAs） are small RNA molecules （～21-24 nt） that play a key role in eukaryotic gene expression regulation. In plants, the majority of microRNAs are encoded by independent transcription units transcribed by RNA polymerase II. Primary transcripts （pri-miRNAs） of miRNA genes （MIRs） undergo extensive co-transcriptional/post-transcriptional processing to generate mature miRNAs.

关键词： MicroRNA 植物累积和 miRNAs 真核细胞聚合酶生成热基因

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Alternative splicing drives the functional diversification of a b HLH transcription factor in the control of growth and drought tolerance in rice

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Science Bulletin 2025年第2期70卷 153-156页

作者： Min Ning Qinyan Li Ya Wang Qingmao Li Yonghong Tao Fan Zhang Fengyi Hu Liyu Huang Key Laboratory of Biology and Germplasm Innovation of Perennial Rice from Ministry of Agriculture and Rural Affairs School of AgricultureYunnan UniversityKunming 650091China Cereal Crops Research Institute Henan Academy of Agricultural SciencesZhengzhou 450002China Wenshan Academy of Agricultural Sciences Wenshan 663000China State Key Laboratory of Crop gene Resources and Breeding Institute of Crop SciencesChinese Academy of Agricultural Sciences(CAAS)Beijing 100081China

Given the increase in global climate change,reconciling the increasing demand for food production with dwindling water resources poses a formidable *** ensure sustainable rice production and global food security,a thorough exploration of the genetic mechanism that underlies the delicate balance between growth and drought tolerance in rice is *** sessile nature of plants has driven their adaptive evolution,enabling them to regulate gene expression and exhibit physiological and developmental plasticity in response to environmental changes[1].Alternative splicing(AS),a prevalent phenomenon in plants,plays a crucial role in the regulation of posttranscriptional gene expression[2].AS serves as an essential mechanism involved in both developmental processes and stress responses[3–5].

关键词： drought mechanism tolerance

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Type-ll Metacaspases Mediate the processing of Plant Elicitor Peptides in Arabidopsis

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Molecular Plant 2019年第11期12卷 1524-1533页

作者： Wenzhong Shen Jiuer Liu Jian-Feng Li State Key Laboratory of Biocontrol Guangdong Provincial Key Laboratory of Plant ResourcesMOE Key Laboratory of Gene Function and RegulationSchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China

Plants can produce animal cytokine-like immune peptides,among which plant elicitor peptides(Peps)derive from the C termini of their precursors(PROPEPs).Recently,the functions of Peps have been expanded beyond plant ***,a long-standing enigma is how PROPEPs are processed into ***,we report that the Ca2+-dependent type-ll metacaspases(MCs)constitute the proteolytic enzymes to mediate PROPEP processing in *** protoplasts,co-expression of PROPEP1 with type-ll MCs,including MC4 to MC9,can promote the generation of processed *** of the catalytic cysteine residue in MC4 or the conserved arginine residue preceding the Pep1 sequence blocks PROPEP1 cleavage,whereas the bacterial elicitor flg22 enhances the MC4-mediated PROPEP1 ***4 cleaves PROPEP1 in vitro and also cleaves PROPEP2 to PROPEP8,but,surprisingly,not PROPEP6 in *** swapping between PROPEP1 and PROPEP6 suggests a hidden role of the sequence context upstream of the Pep sequence for PROPEP ***22-induced PROPEP1 processing and B otrytis cinerea resistance are severely impaired in the m c4/5/6/7 quadruple-mutant *** together,our study identifies the type-ll MCs as new players in Pep signaling,and lays the foundation for understanding the regulation of multifaceted functions of Peps in plant immunity and beyond.

关键词： immunity plant elicitor peptides proteolysis metacaspases Arabidopsis

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Multiplex and optimization of dCas9-TV-mediated gene activation in plants

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Journal of Integrative Plant Biology 2021年第4期63卷 634-645页

作者： Xiangyu Xiong Jieping Liang Zhenxiang Li Ben-Qiang Gong Jian-Feng Li Guangdong Provincial Key Laboratory of Plant Resources State Key Laboratory of BiocontrolMOE Key Laboratory of Gene Function and RegulationSchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China

Synthetic gene activators consisting of nucleasedead Cas9(dCas9)for single-guide RNA(sgRNA)-directed promoter binding and a transcriptional activation domain(TAD)represent new tools for gene activation from endogenous genomic locus in basic and applied plant ***,multiplex gene coactivation by d Cas9-TADs has not been demonstrated in whole *** is also room to optimize the performance of these ***,we report that our previously developed gene activator,dCas9-TV,could simultaneously upregulate OsGW7 and OsER1 in rice by up to 3,738 fold,with one sg RNA targeting to each *** gene coactivation could persist to at least the fourth ***,thepolycistronictRNA-sgRNAexpression under the maize ubiquitin promoter,a Pol II promoter,could cause enormous activation of these genes by up to>40,000-fold in ***,the yeast GCN4 coiled coil-mediated dCas9-TV dimerization appeared to be promising for enhancing gene ***,we successfully introduced a self-amplification loop for dCas9-TV expression in Arabidopsis to promote the transcriptional upregulation of AtFLS2,a previously characterized dCas9-TV-refractory gene with considerable basal ***,this work illustrates the robustness of dCas9-TV in multigene coactivation and provides broadly useful strategies for boosting transcriptional activation efficacy of dCas9-TADs in plants.

关键词： dCas9-TV heritability self-amplification loop multiplex gene coactivation synthetic transcription activator

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Clinicopathological and Prognostic Value of Programmed Cell Death 1 expression in Hepatitis B Virus-related Hepatocellular Carcinoma:A Meta-analysis

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Journal of Clinical and Translational Hepatology 2021年第6期9卷 889-897页

作者： Zi-Yu Zhou Shao-Ru Liu Lei-Bo Xu Chao Liu Rui Zhang Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and gene regulation and Department of Biliary-Pancreatic Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdongChina

Background and Aims:The efficacy of targeted programmed cell death 1/programmed death ligand 1(PD-1/PD-L1)monoclonal antibodies(mAbs)has been confirmed in many solid malignant *** overexpression of PD-1/PD-L1 serves as a biomarker to predict prognosis and clinical ***,the role of PD-1 in patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC)remains *** that HBV is the most important cause for HCC,this study aimed to investigate the prognostic and clinicopathological value of PD-1 in HBV-HCC via a ***:We searched PubMed,Embase,Scopus,the Cochrane Library,Web of Science and Google Scholar up to January 2021 for studies on the correlation between clinicopathology/prognosis and PD-1 in patients with *** pooled hazard ratios(HRs)and 95%confidence intervals(CIs)were calculated to investigate the prognostic significance of PD-1 *** odds ratios(ORs)and 95%CIs were determined to explore the association between PD-1 expression and clinico-pathological ***:Our analysis included seven studies with 658 patients,which showed that high PD-1 expression was statistically correlated with poorer overall survival(HR=2.188,95%CI:[1.262-3.115],pexpression was correlated with multi-ple tumors(OR=2.268,95%CI:[1.209-4.257],p=0.011),high level of alpha fetoprotein(AFP;OR=1.495,95%CI:[1.005-2.223],p=0.047)and advanced Barcelona Clinic Liver Cancer(BCLC)stage(OR=3.738,95%CI:[2.101-6.651],pexpression was associated with multiple tumors,high level of AFP and advanced BCLC *** significantly predicted a poor prognosis of HBV-HCC,which suggests that anti-PD-1 therapy for HBV-HCC patients is plausible.

关键词： Hepatocellular carcinoma Hepatitis B virus Programmed cell death protein 1 Prognosis Clinicopathology

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Establishment of transposase-assisted low-input m^(6)A sequencing technique

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Journal of genetics and Genomics 2021年第11期48卷 1036-1039页

作者： Tao Chen Yan Li Dong-Zhao Ma Zhang Zhang Jian-Fei Xi Guan-Zheng Luo MOE Key Laboratory of gene Function and regulation Guangdong Province Key Laboratory of Pharmaceutical Functional GenesState Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China

RNA modification has been recognized as a pivotal regulator that affects gene expression in a post-transcriptional *** date,more than 150 distinct types of RNA modification have been identi-fied,among which N6-methyladenosine(m6 A)is the most abundant and best-characterized internal modification in mRNAs(Boccaletto et al.,2018).Benefit from the fast development of innovative technologies,the prevalence of m6 A has been reported and confirmed repeatedly in diverse *** studies reveal that aberrant m6 A modification is associated with various disease progressions such as carcinogenesis and tumorigenesis by disturbing the expression of oncogenes and tumor suppressor genes(Tuncel and Kalkan,2019;Zhao et al.,2020).The m6 A methyltransferase METTL3 is found to be overexpressed in acute myeloid leukemia(AML)(Barbieri et al.,2017;Vu et al.,2017),which consequently elevates the m6 A level of B cell lymphoma 2(BCL2)transcript and promotes the translation effi-ciency。

关键词： acute suppressor

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The matrix metalloproteinase stromelysin-3 cleaves laminin receptor at two distinct sites between the transmembrane domain and laminin binding sequence within the extracellular domain

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Cell Research 2005年第3期15卷 150-159页

作者： Tosikazu AMANO,Olivia KWAK,Anastasia MARSHAK Laboratory of gene regulation and Development National Institute of Child Health and Human Development National Institutesof Health Bethesda MD 20892 USA Laboratory of gene regulation and Development National Institute of Child Health and Human Development National Institutesof Health Bethesda MD 20892 USA Laboratory of gene regulation and Development National Institute of Child Health and Human Development National Institutesof Health Bethesda MD 20892 USA

The matrix metalloproteinase (MMP) stromelysin-3 (ST3) has long been implicated to play an important role in extracellular matrix (ECM) remodeling and cell fate determination during normal and pathological processes. However like other MMPs, the molecular basis of ST3 function in vivo remains unclear due to the lack of information on its physiological substrates. Furthermore, ST3 has only weak activities toward all tested ECM proteins. Using thyroid hormone-dependent Xenopus laevis metamorphosis as a model, we demonstrated previously that ST3 is important for apoptosis and tissue morphogenesis during intestinal remodeling. Here, we used yeast two-hybrid screen with mRNAs from metamorphosing tadpoles to identify potential substrate of ST3 during development. We thus isolated the 37 kd laminin receptor precursor (LR). We showed that LR binds to ST3 in vitro and can be cleaved by ST3 at two sites distinct from where other MMPs cleave. Through peptide sequencing, we determined that the two cleavage sites are in the extracellular domain between the transmembrane domain and laminin binding sequence. Furthermore, we demon strated that these cleavage sites are conserved in human LR. These results together with high levels of human LR and ST3 expression in carcinomas suggest that LR is a likely in vivo substrate of ST3 and that its cleavage by ST3 may alter cell-extracellular matrix interaction, thus, playing a role in mediating the effects of ST3 on cell fate and behavior ob- served during development and pathogenesis.

关键词： stromelysin-3 laminin receptor matrix metalloproteinase extracellular matrix Xenopus laevis cell surface substrate.

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Non-viral iPSCs:a safe way for therapy?

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Protein & Cell 2012年第4期3卷 241-245页

作者： Weiqi Zhang Di Guan Jing Qu Weizhou Zhang Guang-Hui Liu National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Laboratory of gene regulation and Signal Transduction Department of PharmacologySchool of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA

Patients-derived induced pluripotent stem cells(iPSCs)pro-vide an invaluable tool to study mechanisms of human dis-eases and also a limitless cellular source for clinical trans-plantation(Takahashi et al.,2007;Yu et al.,2007;Liu et al.,2011a,2011b;Zhang et al.,2012).Retrovirus-or lenti-virus-based delivery systems have been serving as main-stream methods to generate patients-derived ***-ever,genomic integrations of reprogramming factors in virally generated iPSCs not only cause insertional mutagenesis but also lead to residual expression of reprogramming factors in iPSCs and their derivatives.

关键词： al. clinical programming

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Structural analysis of Stc1 provides insights into the coupling of RNAi and chromatin modification

Structural analysis of Stc1 provides insights into the coupl...

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第四届中国结构生物学学术讨论会

作者： Chao He Sreerekha S.Pillai Francesca Taglini Fudong Li Ke Ruan Jiahai Zhang Jihui Wu Yunyu Shi Elizabeth H.Bayne Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences University of Science and Technology of China Wellcome Trust Centre for gene regulation and expression College of Life Sciences University of Dundee

Non-coding RNAs can modulate gene expression by directing modifications to histones that alter chromatin structure. In fission yeast, short interfering（si）RNAs produced via the RNA interference（RNAi） pathway direct modifications associated with heterochromatin formation. siRNAs associate with the RNAi effector protein Ago1, targeting the Ago1-containing RITS complex to homologous nascent transcripts. This promotes recruitment of the H3K9 methyltransferase complex, CLRC, to cognate chromatin. A key question is how the RNAi and chromatin modification machineries are connected. Stc1 is a small protein recently shown to associate with both Ago1 and CLRC, and to play a pivotal role in mediating the RNAi-dependent recruitment of CLRC to chromatin. To understand its mode of action, we have performed a detailed structural and functional analysis of the Stc1 protein. Our analyses reveal that the conserved N-terminal region of Stc1 represents a novel tandem zinc finger domain, with similarities to common LIM domains, but distinguished by a lack of preferred relative orientation of the two zinc fingers. We demonstrate that this tandem zinc finger domain is involved in binding Ago1, while the non-conserved C-terminal region mediates association with CLRC. These findings elucidate the molecular basis for the coupling of RNAi to chromatin modification in fission yeast.

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